85% of sporadic hyperparathyroidism is caused by a solitary adenoma with a surgical cure rate of 90-95%. The remainder of cases have multiple tumors. Of these, about 90% achieve a long remission after their initial operation. Adverse outcomes are increased in multigland disease and in cases with prior failed operation; the adverse outcomes include damage to important structures such as the recurrent laryngeal nerve(s), hypoparathyroidism, persistet hyperparathyroidism, and late recurrent hyperparathyroidism. Approximately half of new referrals to NIH have had prior failed neck exploration for hyperparathyroidism; they have been referred because of our expertise for these cases. The surgical success rate at NIH in these difficult cases has been 95%. This group is enriched for multigland hyperparathyroidism and thus for hereditary causes. Efforts are continuing to improve the methods for preoperative and intra-operative tumor localization in this challenging group. We have successfully decreased the need for invasive methods by obtaining more success from noninvasive methods. Prior failure also increases the likelihood that no normal parathyroid tissue will remain after an otherwise successful operation. Thus cryopreservation and fresh or cryopreserved autografts have been developed to decrease the likelihood of permanent hypoparathyroidism. This program represented the first endocrine tumor imaging program at NIH in the 1960s and continues as a world-wide standard for endocrine tumor imaging and endocrine tumor referrals to NIH.